Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin for thromboprophylaxis after cancer surgery: a systematic review and meta-analysis

Background Direct oral anticoagulants (DOACs) used as an alternative to low-molecular-weight heparin (LMWH) for thromboprophylaxis after cancer surgery for venous thromboembolic events (VTE) remains unclear. This study aimed to investigate the efficacy and safety of DOACs versus LMWH in these patients. Materials and methods A search of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science was carried out and included all randomized controlled trials (RCTs) and observational studies that directly compared DOACs with LMWH for thromboprophylaxis in patients after cancer surgery through July 25, 2023. The primary efficacy and safety outcomes were VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB) within 30 days of surgery. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool for RCTs and ROBINS-I tool for non-randomized studies. This study was registered in PROSPERO (CRD42023445386). Results We retrieved 5149articles, selected 27 for eligibility, and included 10 studies (three RCTs and seven observational studies) encompassing 3054 patients who underwent postoperative thromboprophylaxis with DOACs (41%) or LMWH (59%). Compared to LMWH thromboprophylaxis, DOACs had a comparable risk of VTE (RR:0.69[95% CI:0.46–1.02], I2 = 0%), major bleeding (RR:1.55 [95% CI:0.82–2.93], I2 = 2%), and CRNMB (RR, 0.89 [95% CI, 0.4–1.98], I2 = 31%) during the 30-day postoperative period. Subgroup analysis of VTE and major bleeding suggested no differences according to study type, extended thromboprophylaxis, tumor types, or different types of DOAC. Conclusion DOACs are potentially effective alternatives to LMWH for thromboprophylaxis in patients undergoing cancer surgery, without increasing the risk of major bleeding events. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-024-03341-5.

For Partial Yes: The authors state that they had a written protocol or guide that included ALL the following: For Yes: As for partial yes, plus the protocol should be registered and should also have specified: review question(s) a meta-analysis/synthesis plan, if appropriate, and included/consulted content experts in the field where relevant, searched for grey literature conducted search within 24 months of completion of the review

Did the review authors perform study selection in duplicate?
For Yes, either ONE of the following: at least two reviewers independently agreed on selection of eligible studies and achieved consensus on which studies to include Yes No OR two reviewers selected a sample of eligible studies and achieved good agreement (at least 80 percent), with the remainder selected by one reviewer.

Did the review authors perform data extraction in duplicate?
For Yes, either ONE of the following: at least two reviewers achieved consensus on which data to extract from included studies Yes No OR two reviewers extracted data from a sample of eligible studies and achieved good agreement (at least 80 percent), with the remainder extracted by one reviewer.

Did the review authors provide a list of excluded studies and justify the exclusions?
For Partial Yes: For Yes, must also have: provided a list of all potentially relevant studies that were read in full-text form but excluded from the review Justified the exclusion from the review of each potentially relevant study

For Yes
Must have reported on the sources of funding for individual studies included in the review.Note: Reporting that the reviewers looked for this information but it was not reported by study authors also qualifies Yes No

RCTs
For Yes: The authors justified combining the data in a meta-analysis Yes No No meta-analysis conducted AND they used an appropriate weighted technique to combine study results and adjusted for heterogeneity if present.

AND investigated the causes of any heterogeneity
For NRSI For Yes: The authors justified combining the data in a meta-analysis Yes No No meta-analysis conducted AND they used an appropriate weighted technique to combine study results, adjusting for heterogeneity if present AND they statistically combined effect estimates from NRSI that were adjusted for confounding, rather than combining raw data, or justified combining raw data when adjusted effect estimates were not available AND they reported separate summary estimates for RCTs and NRSI separately when both were included in the review 12.If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis?
For Yes: included only low risk of bias RCTs Yes No No meta-analysis conducted OR, if the pooled estimate was based on RCTs and/or NRSI at variable RoB, the authors performed analyses to investigate possible impact of RoB on summary estimates of effect.

Did the review authors account for RoB in individual studies when interpreting/ discussing the results of the review?
For Yes: included only low risk of bias RCTs Yes No OR, if RCTs with moderate or high RoB, or NRSI were included the review provided a discussion of the likely impact of RoB on the results

Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review?
For Yes: There was no significant heterogeneity in the results

Yes No
OR if heterogeneity was present the authors performed an investigation of sources of any heterogeneity in the results and discussed the impact of this on the results of the review 15.If they performed quantitative synthesis did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?
For Yes: performed graphical or statistical tests for publication bias and discussed the likelihood and magnitude of impact of publication bias Yes No No meta-analysis conducted 16.Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?
For Yes: the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?
the review authors explain their selection of the study designs for inclusion in the review?For Yes, the review should satisfy ONE of the following: Explanation for including only RCTs Yes No OR Explanation for including only NRSI OR Explanation for including both RCTs and NRSI 4. Did the review authors use a comprehensive literature search strategy?For Partial Yes (all the following):For Yes, should also have (all the following